MicroRNA-506 suppresses tumor proliferation and metastasis in colon cancer by directly targeting the oncogene EZH2
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Yi Zhang1,2,*, Changwei Lin3,*, Guoqing Liao1, Sheng Liu1, Jie Ding4, Fang Tang5, Zhenran Wang5, Xingsi Liang5, Bo Li5, Yangchao Wei5, Qi Huang5, Xuan Li5, Bo Tang5
1Department of Gastrointestinal Surgery, Xiangya Hospital, Central South University, 410008, PR China
2Department of Oncological Surgery, Affiliated Hospital of Xuzhou Medical College, 221000, PR China
3Department of Gastrointestinal Surgery, Third Xiangya Hospital, Central South University, 410008, PR China
4Department of Gastrointestinal Surgery, Guizhou Provincial People's Hospital, 550000, PR China
5Department of Hepatobiliary Surgery, Affiliated Hospital of Guilin Medical University, 541000, PR China
*These authors have contributed equally to this work
Guoqing Liao, e-mail: [email protected]
Bo Tang, e-mail: [email protected]
Keywords: miR-506, EZH2, proliferation, metastasis, colon cancer
Received: March 27, 2015 Accepted: September 21, 2015 Published: October 03, 2015
Increasing evidence reveals that aberrant expression of microRNA contributes to the development and progression of colon cancer, but the roles of microRNA-506 (miR-506) in colon cancer remain elusive. Here, we demonstrated that miR-506 was down-regulated in colon cancer tissue and cells and that miR-506 expression was inversely correlated with EZH2 expression, tumor size, lymph node invasion, TNM stage and metastasis. A high level of miR-506 identified patients with a favorable prognosis. In vitro and in vivo experiments confirmed that miR-506 inhibits the proliferation and metastasis of colon cancer, and a luciferase reporter assay confirmed that EZH2 is a direct and functional target of miR-506 via the 3′UTR of EZH2. The restoration of EZH2 expression partially reversed the proliferation and invasion of miR-506-overexpressing colon cancer cells. Moreover, we confirmed that the miR-506-EZH2 axis inhibits proliferation and metastasis by activating/suppressing specific downstream tumor-associated genes and the Wnt/β-catenin signaling pathway. Taking together, our study sheds light on the role of miR-506 as a suppressor for tumor growth and metastasis and raises the intriguing possibility that miR-506 may serve as a new potential marker for monitoring and treating colon cancer.
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